title: Enhanced constitutive invasion activity in human nontumorigenic keratinocytes exposed to a low level of barium for a long time.
abstract: We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion.
authors.affiliation: Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Kasugai-shi, Aichi, 487-8501, Japan; Department of Biochemistry and Plant Biology, Vietnam National University, Hanoi, Vietnam.
authors.forename: Nguyen D
authors.initials: ND
authors.lastname: Thang
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yajima
authors.forename: Shoko
authors.initials: S
authors.lastname: Ohnuma
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Ohgami
authors.forename: Mayuko Y
authors.initials: MY
authors.lastname: Kumasaka
authors.forename: Gaku
authors.initials: G
authors.lastname: Ichihara
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
mesh_terms: D001464:Barium / Q000032:analysis / Q000633:toxicity*; D002460:Cell Line; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D061251:Primary Cell Culture; D014744:Vietnam; D014877:Water Pollution, Chemical / Q000009:adverse effects* / Q000032:analysis; D014881:Water Supply / Q000032:analysis
chemical_list: D001464:Barium; D051417:Focal Adhesion Kinase 1; D053511:Matrix Metalloproteinase 14
keywords: barium; focal adhesion kinase; invasion; keratinocytes; matrix metalloproteinase; well water